Methods of treatment comprising administration of Substance P

ABSTRACT

A method for treatment of symptoms of a respiratory disease or pain in a subject comprising administering to said subject a Substance P in an amount effective to alleviate those symptoms.

BACKGROUND OF THE INVENTION

[0001] Substance P is a protein naturally occurring in the body. It is atachykinin which induces contraction of smooth muscle and appears inhumans and other mammals at highest concentrations in brain, intestine,spinal ganglia.

[0002] Since the late 1970's, studies have shown that Substance P has avariety of biological activities including acting as a vasodilator,stimulates salivation, can cause increased gut permeability. Ofparticular interest to the present invention is the observation thatSubstance P can, at different concentrations, cause analgesia orhyperalgesia. Although its biological activity can be difficult tomeasure, its activity as a systemic signal is highly stable at ambientand refrigerated temperatures.

[0003] Substance P can act as a neurotransmitter or a hormone(particularly in the gut as a hormone). The vasodilation caused bySubstance P is a result of its direct inhibitory effect on arteriolarsmooth muscle. This effect is mediated by receptors that appear specificto Substance P versus other vasodialators. Of interest to the presentinvention is that those receptors appear to be identical to thosespecific for rubeola virus. While Substance P inhibits contraction ofarteriolar smooth muscle, it stimulates contraction of intestinal,bronchial and venous smooth muscle. Substance P can also cause diuresisand natriuresis in kidneys. These observations suggest that there couldbe more than one type of Substance P receptor.

SUMMARY OF THE INVENTION

[0004] The present invention relates to the observation that Substance Pappears to be a signal for the mediation of neurogenic pain and that itwould appear to be a candidate as a therapeutic agent for those types ofpain which are most difficult to control, especially peripheralneuropathy.

[0005] The present invention provides methods for treatment of diseasestates selected from the group consisting of respiratory dysfunction andpain comprising administration of an effective amount of Substance P.The invention also provides pharmaceutical compositions for treatment ofrespiratory dysfunction and pain comprising an effective amount ofSubstance P in combination with a suitable carrier.

[0006] It is believed that Substance P may function in the treatment ofpain by having a direct effect on pain receptors. Moreover, while notwishing to be bound by any particular theory of the invention, SubstanceP may operate in treatment of certain respiratory conditions such asReactive Upper Airway Dysfunction (RUDS) through a mechanism oftreatment of neuropathy. Specifically, RUDS has been described as acranial nerve neuropathy involving the 10th cranical nerve (vagus).Accordingly, it may be that Substance P treats respiratory conditionssuch as RUDS through a mechanism which treats neuropathies associatedwith those diseases.

[0007] An effective amount of Substance P according to the invention isan amount which results in a reduction in the symptoms of a respiratorydisease or of pain symptoms. Amounts of Substance P ranging from 10⁻⁷ to10⁻² mg are contemplated to be effective according to the invention.While preferred dosages include those ranging from 10⁻⁵ to 10⁻⁴ mgSubstance P and 8×10⁻⁵ mg has been found to be particulary effectivewhen administered from one to six times daily in the form of sublingualdrops, those of ordinary skill would be capable of adjusting the dosageamounts and schedule by observation of the effectiveness of treatment.Accordingly, it is contemplated that the range in dosage for theapplication could be several logs higher or lower than the optimumabove. While the preferred route of administration is sublingualadministration, it would be apparent to those of skill in the art thatother routes would also be suitable for treatment according to theinvention including subcutaneous administration, intramuscular,intravenous administration and the like. The invention also providespharmaceutical compositions for treatment of respiratory conditions andpain comprising Substance P in combination with a suitable carrier suchas saline or other pharmaceutically acceptable excipients.

DETAILED DESCRIPTION OF THE INVENTION EXAMPLE 1

[0008] According to this example, a male presented with upper airwaydistress who had a persistent cough triggered by exposure to volatilechemicals. His disease appeared to be initiated by chronic exposure tofloor stripper which caused RUDS (Reactive Upper Airway Dysfunction).This cough was stopped almost immediately by treatment with Substance Pwhich was administered by sublingual drop (0.05 ml/drop) at one drop perhour for three hours and then one drop four times daily. Each dropcontained 8×10⁻⁵ mg synthetic Substance P (Sigma) in phosphate bufferedsaline.

EXAMPLE 2

[0009] According to this example, an 8 year old boy presented with arepetitive, almost tic-like, exaggerated cough that was disruptive tohis classmates and teacher. Several physicians were consulted withoutsuccess and with no apparent cause found for the cough. Substance P wasadministered by sublingual administration according to the method ofExample 1 and stopped the cough within minutes. Practice of the methodof the invention continued to control this disorder after more than ayear.

EXAMPLE 3

[0010] According to this example, a 49 year old female presented RUDSthat manifested as severe hoarseness or even aphonia if exposed tovolatile chemicals, and especially to fragrances. She had suffered forseveral years after being exposed to fragrances from several co-workersusing multiple perfumes. Her airway problem was reduced only by completeavoidance of any exposure to volatile chemicals which dramaticallychanging her lifestyle. Sublingual administration of Substance Paccording to the method of Example 1 provided significant improvementand has allowed her to return to more normal living. Her RUDS continuesto be controlled by taking one drop of Substance P four times daily, ormore frequently if needed.

EXAMPLE 4

[0011] According to this example, a 63 year old woman presented with ahistory of numbness, tingling and severe pain in feet and legs eightyears earlier. During the year immediately preceding her first officevisit, the discomfort had spread to her hands. She had a history offamilial diabetes, but she did not test diabetic. No cause of herdiscomfort could be determined, and the only relief she obtained wasfrom narcotic analgesics.

[0012] The subject was treated by sublingual administration of SubstanceP according to the method of Example 1 and she experienced almostimmediate pain relief. As a result, the subject was able to discontinuenarcotics, and continues well with continued Substance P treatment.

EXAMPLE 5

[0013] According to this example, a 69 year old woman presented withsevere sciatic-like pain of the hip of long duration. The subject alsopresented with a diagnosis of diabetes. The subject was treated bysublingual administration of Substance P according to the method ofExample 1 which reduced the pain dramatically. She continues well forover two years.

EXAMPLE 6

[0014] According to this example, a 44 year old female presented with adiagnosis of chronic sciatic pain that was disabling and of severalyears duration. Analgesics helped reduce the pain. The subject wastreated by sublingual administration of Substance P according to themethod of Example 1. The first sublingual drop of Substance P instantlyand dramatically “turned off” the pain. The Patient continued overseveral months to use daily doses of Substance P with continued controlof pain.

EXAMPLE 7

[0015] According to this example, a 59 year old woman witharthritis-like pain and inflammation of the knuckles but who testednegative for rheumatoid factor. Pain was not significantly reduced byover the counter formulations or prescription drugs. The subject wastreated by sublingual administration of Substance P according to themethod of Example 1. After three days of Substance P sublingual droptherapy, the patient reported “remarkable” improvement that continuedafter two months.

[0016] Numerous modifications and variations in the practice of theinvention are expected to occur to those skilled in the art uponconsideration of the presently preferred embodiments thereofConsequently, the only limitations which should be placed upon the scopeof the invention are those which appear in the appended claims.

What is claimed:
 1. A method for the treatment of symptoms of arespiratory disease or pain in a subject comprising administering tosaid subject a Substance P in an amount effective to alleviate thosesymptoms.
 2. The method of claim 1 wherein said respiratory disease isReactive Upper Airway Dysfunction.
 3. The method of claim 1 wherein thedisease is neurogenic pain.
 4. The method of claim 1 wherein the diseaseis peripheral neuropathy.
 5. The method of claim 1 wherein Substance Pis administered by a route selected from the group consisting ofsublingual administration and subcutaneous administration.
 6. The methodof claim 5 wherein Substance P is administered by sublingualadministration.
 7. The method of claim 6 wherein Substance P isadministered at a dosage of from 10⁻⁵ to 10⁻⁴ mg one to six times daily.8. A pharmaceutical composition for treatment of symptoms of arespiratory disease or pain in a subject comprising Substance P in anamount effective to alleviate those symptoms and a suitable carrier. 9.The pharmaceutical composition of claim 8 wherein the Substance P ispresent in a dosage of from 10⁻⁵ to 10⁻⁴ mg.